More than 10 million people worldwide suffer from Parkinson's disease, and more than 50% of them ill suffer from mental disorders (mainly hallucinations and illusions). Mental symptoms are very common in patients with Parkinson's disease, that is very distressed to take care of them. Mental illness is the main driving factor for Parkinson's patients to be sent to sanatoriums, which greatly increases the risk of death. At present, the only alternative treatment is dopamine antagonists such as clozapine and quetiapine, which may aggravate motor symptoms, accelerate cognitive impairment, increase the risk of stroke and even endanger life even if they are used for a short time.
Compound 1, Pimavanserin tartrate, (N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-[4-(2-methylpropoxy)phenylmethyl]urea tartrate) is a drug approved by the US FDA under the trade name NUPLAZID. The drug was developed by Acadia Pharmaceuticals. It is suitable for the treatment of hallucinations and delusions associated with Parkinson's disease. Pimavanserine works by blocking the serotonin 2A receptor on the neocortex, which is the brain region responsible for sensory, awake thinking and language, as well as visual hallucinations and illusions. The discovery and application of Pimavanserine opens up new avenues for the treatment of Parkinson's disease. Because of its potentially good safety, pimavanserine may help treat patients with Parkinson's disease and mild psychiatric symptoms, help prevent more troublesome symptoms, and target psychiatric symptoms of other diseases, such as Alzheimer's disease.
Pimavanserin has potential for the treatment of diseases such as: psychosis, schizophrenia, schizoaffective disorder, mania, psychosis, affective disorder, dementia, anxiety, sleep disorders, appetite disorders, double Phase-related mental disorders, psychosis secondary to hypertension, migraine, vasospasm and ischemia, motor convulsions, tremors, psychomotor retardation, bradykinesia and psychotic pain, Parkinson's, Huntington's disease, Alzheimer's Disease, spinal cerebellar atrophy, Tourette's syndrome, Friedreich's ataxia, Machado-Joseph's disease, Lewy body dementia, progressive supranuclear palsy and frontotemporal dementia, myoclonus, or tremor, myocardial infarction, thrombotic or ischemic stroke, idiopathic and thrombotic thrombocytopenic purpura, peripheral vascular disease, and Raynaud's disease.
Pimavanserin has a molecular formula of C25H34FN3O2 and a molecular weight of 427.5. The chemical structure of Pimavanserin is as follows:

Chemical raw materials of active pharmaceutical ingredients (API) must have good purity, stability, physical and chemical properties and operability. These properties are related to the crystalline form of the drug, and different crystal forms have different physical and chemical properties. The purpose of improving the stability of the drug preservation and the efficacy of the drug, it is necessary to make the raw API into crystal form.
A drug may exist in a plurality of crystalline forms, and different crystal forms of the same drug may have different dissolution and absorption in the body, thereby affecting the dissolution and release of the formulation.
The optimal crystalline form can be discovered by thoroughly studying of the polymorphism of the compound. The optimal crystalline form is crucial to the efficacy of the drug and the formulation process which is based on the characteristics of the crystalline form, thereby effectively ensuring the equivalence of the drug batch to batch.
Drug powder flowability is also an important factor throughout the pharmaceutical formulation process. When the powder or the capsule formulation was prepared by directly mixing and filling, components are difficult to mix uniformly and affect the exact content of the drug product due to poor powder flowability. In the process of compressing or filling of granules, tablets, capsules, etc., the particles with poor flowability tend to make the surface rough of drug product or not easy to dispersible of the drug which lead to inconvenient for patients to take. Poor flowability of the drug powder also affects the smooth process and increase the cost of the drug product preparation. In the application of external powder topical formulation, the powder with poor powder flowability will lead to unevenly coated of the drug resulting in excessive or excessive topical application, which finally affecting the efficacy of the drug. In the storage and transportation of the preparation, the formulation made of the powder with poor fluidity is more susceptible to the influence of ambient temperature, humidity, pressure, mechanical force and the like to reduce the stability and effectiveness of the drug.
Angle of repose is adopted widely to evaluate the powder flowability. When the angle of repose of the powder is less than or equal to 30 degrees, it means the flowability of this powder is good. While in case, 40 degrees or less of the powder angle of repose, this powder can satisfy the demand for fluidity in the production process. When the angle of repose of the powder is more than 40 degrees, it means the very poor flowability of the drug powder which may cause the troubles above mentioned during the drug manufacturing process.